Abstract

Vitamin C significantly reduced senescence-associated β-galactosidase (SA-β-gal) activity, with both the suppression of cell-cycle inhibitors (p53, p21, p16, and pRb) and stimulation of cell-cycle activators (E2F1 and E2F2). Vitamin C also effectively attenuated the hyperactivation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase-B (AKT) signaling pathway. The expression of the longevity marker, the mammalian target of rapamycin (mTOR), was down-regulated by vitamin C while the expressions of forkhead box O3a (FoxO3a) and sirtuin1 (SIRT1) were up-regulated by vitamin C. In the middle-aged (MA) mice, oral administration of vitamin C significantly inhibited wrinkle formation, skin atrophy, and loss of elasticity through increasing collagen and elastic fiber. The increase in transepidermal water loss and the decrease in skin hydration were recovered by vitamin C treatment in the MA mice. Overall, vitamin C effectively prevents cellular senescence in vitro and in vivo suggesting it has protective potential against natural aging of the skin.